Pre-eclampsia is associated with an excess of proliferative immature intermediate trophoblast

Pre-eclampsia/toxemia (PET) is an idiopathic hypertensive disorder of pregnancy elicited in susceptible mothers by exposure to placental trophoblast. Three facts regarding the placenta in PET are known: an association with large placentas (excessive trophoblast), a tendency for superficial implantation, and inappropriate trophoblastic immaturity, as assessed by ultrastructural and biochemical criteria. A unitary hypothesis is that PET is related to a maturation defect leading to excessive accumulation of inappropriately immature intermediate trophoblast in the placental implantation site. We studied the implantation site of PET and control placentas from three gestational age groups (25 to 30, 30 to 35, and 36 to 40 weeks old [five per group]) by morphometry and immunohistochemistry using antibodies to three phenotypic markers (cytokeratin, human placental lactogen (HPL), and beta 2-microglobulin) and two markers of cell dynamics (proliferating cell nuclear antigen [PCNA] and bcl-2]). Implantation sites in the PET group had increased amounts of intermediate trophoblast (cell number and longitudinal extent) with an increased proliferative index (percentage of PCNA positive) and evidence of phenotypic immaturity (HPL negative). Intermediate trophoblast from both groups was uniformly bcl-2 negative and beta 2-microglobulin positive. Based on these data and the findings of other investigators, we propose that the diagnostic term "atypical implantation site" be added to acute atherosis, villous infarction, and increased syncytial knotting as a characteristic of placentas from pre-eclamptic pregnancies.